The present invention provides a new use for some known compounds. More particularly, the present invention provides a method for preventing renal papillary necrosis induced by non-steroidal anti-inflammatory compounds (NOSAC) by the administration of certain prostaglandins.
Renal papillary necrosis is a condition of the kidneys which is associated with the administration of NOSAC. Originally, renal papillary necrosis was thought to be a form of fulminating pyelonephritis. See, e.g., Morales, et al., Arch. Surg. 103:420 (1971). However, it has also been found to be associated with the administration of various analgesic compounds. See, Spuhler, et al., Z. Klin. Med. 151:1-50 (1953). Renal papillary necrosis is characterized by morpholosical changes and renal failure as a consequence of damage to the renal papillae. Renal papillary necrosis has been associated with phenylbutazone (see Morales, supra); phenacetin (see, e.g., Burry, et al., Med. J. Aust., 1:31-36 (1974)); indomethacin (Arnold, et al., Pathology 6:303-313 (1974)), aspirin (see Arnold, supra); amidopyrine (see Arnold, supra) and the like. Renal papillary necrosis is thus a serious problem associated with the administration of non-steroidal anti-inflammatory compounds.
The prostaglandins are derivatives of prostanoic acid, having the carbon atom numbering and structure as shown in Formula I. A trivial system of nomenclature has been devised, which classifies the prostaglandins according to these substituents on the cyclopentane ring. See, N. A. Nelson, Journal of Medicinal Chemistry, 17:911 (1974). For a discussion of the uses of the prostaglandins, see, e.g., N. A. Nelson, et al., Chemical and Engineering News, pp. 30-44 (Aug. 16, 1982).
Pharmacological agents which prevent necrotic changes in cells are known as cytoprotective agents. Numerous gastrointestinal cytoprotective effects of the prostaglandins are known. See for example, U.S. Pat. No. 4,083,998 (Robert, "Treatment of Inflammatory Disease of the Mammalian Large Intestine with Cytoprotective Prostaglandins"), issued Apr. 11, 1978, U.S. Pat. No. 4,081,553 (Robert, Cytoprotective Prostaglandins for Use in Intestinal Diseases"), issued Mar. 28, 1978, and U.S. Pat. No. 4,097,603 (Robert, "Gastric Cytoprotection with Non-Antisecretory Doses of Prostaglandins"), issued June 27, 1978.